1. Acquisition of heroin conditioned immunosuppression requires IL-1 signaling in the dorsal hippocampus.
- Author
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Lebonville CL, Jones ME, Hutson LW, Cooper LB, Fuchs RA, and Lysle DT
- Subjects
- Animals, Behavior, Animal drug effects, Behavior, Animal physiology, Disease Models, Animal, Heroin administration & dosage, Interleukin 1 Receptor Antagonist Protein administration & dosage, Male, Narcotics administration & dosage, Rats, Rats, Inbred Lew, Conditioning, Psychological drug effects, Conditioning, Psychological physiology, Heroin pharmacology, Hippocampus drug effects, Hippocampus immunology, Hippocampus metabolism, Immunosuppression Therapy, Interleukin 1 Receptor Antagonist Protein pharmacology, Interleukin-1 metabolism, Narcotics pharmacology, Signal Transduction
- Abstract
Opioid users experience increased incidence of infection, which may be partially attributable to both direct opiate-immune interactions and conditioned immune responses. Previous studies have investigated the neural circuitry governing opioid conditioned immune responses, but work remains to elucidate the mechanisms mediating this effect. Our laboratory has previously shown that hippocampal IL-1 signaling, specifically, is required for the expression of heroin conditioned immunosuppression following learning. The current studies were designed to further characterize the role of hippocampal IL-1 in this phenomenon by manipulating IL-1 during learning. Experiment 1 tested whether hippocampal IL-1 is also required for the acquisition of heroin conditioned immunosuppression, while Experiment 2 tested whether hippocampal IL-1 is required for the expression of unconditioned heroin immunosuppression. We found that blocking IL-1 signaling in the dorsal hippocampus with IL-1RA during each conditioning session, but not on interspersed non-conditioning days, significantly attenuated the acquisition of heroin conditioned immunosuppression. Strikingly, we found that the same IL-1RA treatment did not alter unconditioned immunosuppression to a single dose of heroin. Thus, IL-1 signaling is not a critical component of the response to heroin but rather may play a role in the formation of the association between heroin and the context. Collectively, these studies suggest that IL-1 signaling, in addition to being involved in the expression of a heroin conditioned immune response, is also involved in the acquisition of this effect. Importantly, this effect is likely not due to blocking the response to the unconditioned stimulus since IL-1RA did not affect heroin's immunosuppressive effects., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2016
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